WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature (original) (raw)

• Letter
• Published: 15 September 2005
• Sujata Rao1 na1,
• Thomas J. Carroll2 nAff7,
• Jefferson E. Vallance1,
• Masataka Ito3,
• Jennifer K. Ondr1,
• Savita Kurup1 nAff8,
• Donald A. Glass4,
• Millan S. Patel4,
• Weiguo Shu5,
• Edward E. Morrisey5,
• Andrew P. McMahon2,
• Gerard Karsenty4 &
• …
• Richard A. Lang1

Nature volume 437, pages 417–421 (2005)Cite this article

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Abstract

Macrophages have a critical role in inflammatory and immune responses through their ability to recognize and engulf apoptotic cells1. Here we show that macrophages initiate a cell-death programme in target cells by activating the canonical WNT pathway. We show in mice that macrophage WNT7b is a short-range paracrine signal required for WNT-pathway responses and programmed cell death in the vascular endothelial cells of the temporary hyaloid vessels of the developing eye. These findings indicate that macrophages can use WNT ligands to influence cell-fate decisions—including cell death—in adjacent cells, and raise the possibility that they do so in many different cellular contexts.

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Acknowledgements

We thank: P. Speeg for technical assistance; E. Fuchs, L. Niswander and C. Dean for the TOPGAL mice; S. McKercher and R. Maki for the _PU.1_-null mice; L. Chan for the _Lrp5_-null mice; and, R. Grosschedl for the _Lef1_-null mice. We are indebted to Q. Xu and J. Nathans for providing the SuperTOPFLASH cell line and for the Fzd and Norrin expression plasmids. This work was supported by NIH grants to E.E.M., A.P.M., G.K. and R.A.L. G.K. was also supported by funds from the March of Dimes, and R.A.L. by funds from the Abrahamson Pediatric Eye Institute Endowment at the Children's Hospital Medical Center of Cincinnati.

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Author notes

1. Ivan B. Lobov
   Present address: Regeneron Pharmaceuticals, Tarrytown, New York, 10591, USA
2. Thomas J. Carroll
   Present address: University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas, 75390, USA
3. Savita Kurup
   Present address: Department of Medicine, University of Sydney, New South Wales, 2006, Australia
4. Ivan B. Lobov and Sujata Rao: *These authors contributed equally to this work

Authors and Affiliations

1. Division of Developmental Biology, The Children's Hospital Research Foundation and Department of Ophthalmology, University of Cincinnati, Ohio, 45229, Cincinnati, USA
   Ivan B. Lobov, Sujata Rao, Jefferson E. Vallance, Jennifer K. Ondr, Savita Kurup & Richard A. Lang
2. Department of Molecular and Cellular Biology, Harvard University, Massachusetts, 02138, Cambridge, USA
   Thomas J. Carroll & Andrew P. McMahon
3. Department of Anatomy, National Defense Medical College, 359-8513, Tokorozawa, Japan
   Masataka Ito
4. Department of Molecular and Human Genetics, Baylor College of Medicine, Texas, 77030, Houston, USA
   Donald A. Glass, Millan S. Patel & Gerard Karsenty
5. Department of Medicine and Molecular Cardiology Research Center, University of Pennsylvania, Pennsylvania, 19104, Philadelphia, USA
   Weiguo Shu & Edward E. Morrisey

Authors

1. Ivan B. Lobov
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2. Sujata Rao
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3. Thomas J. Carroll
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4. Jefferson E. Vallance
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5. Masataka Ito
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6. Jennifer K. Ondr
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7. Savita Kurup
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8. Donald A. Glass
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9. Millan S. Patel
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10. Weiguo Shu
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11. Edward E. Morrisey
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12. Andrew P. McMahon
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13. Gerard Karsenty
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14. Richard A. Lang
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Corresponding author

Correspondence toRichard A. Lang.

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Supplementary information

Supplementary Figure S1

Pupillary membrane persistence in the PU.1 mutant mouse. Pupillary membrane is persistent in the PU.1 mutant mouse. (PDF 830 kb)

Supplementary Figure S2

Assessment of Wnt pathway stimulation by, and Wnt gene expression in, hyaloid macrophages. This figure shows that macrophages can stimulate cellular responses in hyaloid VECs that are characteristic of Wnt pathway responses and that macrophages can express Wnt ligand genes. (PDF 746 kb)

Supplementary Figure S3

Generation of the Wnt7b _d1_allele. This figure shows the gene-targeting scheme for generation of the Wnt7b d1 allele. (PDF 67 kb)

Supplementary Figure S4

Assessment of Fzd receptors in mediating Wnt7b signalling. Supplementary Figure S4 shows that Fzd4 can mediate Wnt7b signalling and that Fzd4 is expressed in the hyaloid capillaries. (PDF 227 kb)

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Lobov, I., Rao, S., Carroll, T. et al. WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature.Nature 437, 417–421 (2005). https://doi.org/10.1038/nature03928

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• Received: 18 January 2005
• Accepted: 10 June 2005
• Issue Date: 15 September 2005
• DOI: https://doi.org/10.1038/nature03928

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